High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

• Main Authors: Detterbeck Frank, Gettinger Scott, Boffa Daniel, Tanoue Lynn, Frangia Konstantina, Panagopoulos Nikolaos, Liceaga Camil, Gopinath Arun, Tzelepi Vassiliki, Zolota Vassiliki, Lowery Frank J, Anagnostou Valsamo K, Homer Robert J, Dougenis Dimitrios, Rimm David L, Syrigos Konstantinos N
• Format: Article
• Language: English
• Published: BMC 2010-05-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/10/186

<p>Abstract</p> <p>Background</p> <p>Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.</p> <p>Methods</p> <p>Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA^®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome.</p> <p>Results</p> <p>Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005).</p> <p>Conclusions</p> <p>Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.</p>